Advances in the genetic understanding of hypohidrotic ectodermal dysplasia

Introduction: Ectodermal dysplasia refers to the abnormal development of two or more embryological elements that give rise to skin, hair, teeth, and sweat glands. Clinically, ectodermal dysplasia can be phenotypically diverse with >200 different syndromes documented in the literature based on ascertainment of particular developmental anomalies.Area covered: The most common subtype is hypohidrotic ectodermal dysplasia which occurs in ~7 per 10,000 live births. Most cases of hypohidrotic ectodermal dysplasia are X-linked, although autosomal dominant and autosomal recessive cases may occur, and mutations in four genes have been implicated in this form of ectodermal dysplasia: EDA, EDAR, EDARADD, and WNT10A.Expert opinion: The protean nature of ectodermal dysplasia makes clinical or mechanistic classification challenging but identification of causative gene pathologies in ~30% of all ectodermal dysplasias, including the vast majority of hypohidrotic ectodermal dysplasia cases, has improved diagnostic precision, made DNA-based prenatal diagnosis possible, and advanced translational research, including the clinical testing of recombinant proteins targeting the inherent molecular pathology in a subgroup of affected individuals.